Case #17: Every Cure Pt.1 (Dr. David Fajgenbaum)

Summary

Symptomatic: A Medical Mystery Podcast – Episode Summary: "Case #17: Every Cure Pt.1 (Dr. David Fajgenbaum)"

In this compelling episode of Symptomatic: A Medical Mystery Podcast, hosted by Lauren Bright Pacheco, listeners are introduced to the harrowing yet inspiring journey of Dr. David Fajgenbaum. This episode delves deep into David's battle with Castleman Disease, a rare and aggressive condition, and his relentless quest to find a cure not only for himself but for others suffering from similar afflictions.

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1. Early Life and Aspirations

David Fajgenbaum's story begins in Raleigh, North Carolina, where he grew up as the youngest child in a dedicated family. His parents, immigrants from Trinidad and Tobago, instilled in him the values of hard work and perseverance.

[01:36] David Fajgenbaum: "I wanted to play quarterback, and I wanted to play Division 1 college football. That was like my first dream. And that is all I could think about for about a decade."

From a young age, David demonstrated exceptional dedication, becoming a star high school quarterback. Inspired by his father, an orthopedic surgeon who worked with the North Carolina State Wolf Pack, David aspired to excel both academically and athletically.

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2. Impact of His Mother's Illness

David's life took a dramatic turn during his freshman year at Georgetown University when his mother was diagnosed with brain cancer. This pivotal moment not only altered his personal trajectory but also fueled his passion for medicine.

[04:45] David Fajgenbaum: "It completely shaped my desire to become a doctor... this is what I have to spend the rest of my life doing."

Witnessing his mother's courageous battle against cancer ignited David's commitment to alleviating suffering and finding effective treatments for debilitating diseases.

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3. Medical School and Onset of Symptoms

While pursuing his medical degree at the University of Pennsylvania, David maintained his dedication to physical fitness, earning the nickname "the Beast" for his athletic prowess. However, during his third year, unexpected and severe health issues began to surface.

[08:22] David Fajgenbaum: "Fatigue became this fatigue that I'd never experienced before... I knew something really bad was happening."

Symptoms such as extreme fatigue, lumps in his neck, and fluid retention signaled that something was amiss. Despite his medical knowledge, David struggled to comprehend his own deteriorating health.

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4. The Diagnostic Odyssey: From Lymphoma to Castleman Disease

David's rapid decline led to multiple hospitalizations, where a series of exhaustive tests failed to pinpoint the exact cause of his symptoms. Initially suspecting aggressive lymphoma, the eventual diagnosis revealed a rare form of Castleman Disease.

[14:09] David Fajgenbaum: "I thought, maybe it's not autoimmune disease. But none of the autoimmune disease tests were coming back."

Castleman Disease, characterized by an overactive immune system, was both a relief and a new source of uncertainty for David and his family. The rarity of the condition meant limited treatment options and a bleak prognosis.

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5. Struggles and Support During Hospitalizations

Throughout his battle, David faced multiple relapses and aggressive treatments that took a significant toll on his body. The unwavering support from his family, particularly his wife Caitlin and his friend Grant Mitchell, played a crucial role in his fight for survival.

[16:37] Grant Mitchell: "I couldn't hide how horrifying it was to see him in that state."

The emotional and physical challenges were immense, but David's determination to honor his mother's legacy and his own commitment to medicine kept him pushing forward.

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6. Pursuit of Alternative Treatments and Research

After exhausting standard treatment avenues, David embarked on a daring plan to test experimental drugs on himself. His research led him to sirolimus, an MTOR inhibitor, which showed promise in controlling his disease.

[25:12] David Fajgenbaum: "What if there's some other drug out there that wasn't made for Castleman disease... could save my life?"

This approach was unconventional and fraught with risk, but it exemplified David's innovative spirit and refusal to succumb to his illness.

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7. Turning Point: Achieving Remission

David's experimental treatment with sirolimus marked a significant turning point in his battle against Castleman Disease. After enduring multiple relapses and aggressive chemotherapies, this newfound therapy brought him into remission.

[37:02] David Fajgenbaum: "It's because we connected on that last one that I'm still here and that now I can continue to pursue this for other people."

The successful remission not only saved David's life but also paved the way for future research and treatment protocols for Castleman Disease.

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8. Legacy and Continued Mission

David's journey didn't end with his remission. Inspired by his own experience, he founded the Castleman Disease Collaborative Network (CDCN), aiming to connect researchers and accelerate the discovery of effective treatments.

[27:17] David Fajgenbaum: "Can I figure out what's going wrong in my body and then can I figure out, is there a drug that's already FDA approved for some other disease that might actually be able to be useful for my disease that I thought could save my life?"

His proactive approach highlights the critical importance of patient-led research and the potential of repurposing existing drugs to tackle rare diseases.

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9. Personal Reconciliation and Future Outlook

As David regained his health, he and Caitlin found solace in their rekindled relationship, culminating in their wedding—a testament to their resilience and unwavering support for each other.

[35:05] Caitlin: "It was so powerful... We had already been through it. It just meant so much to us."

Looking ahead, David remains committed to his mission of finding cures for rare diseases, driven by his personal experiences and the lives he touched during his struggle.

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Conclusion

"Case #17: Every Cure Pt.1" is a profound narrative of survival, love, and the relentless pursuit of medical breakthroughs. David Fajgenbaum's story underscores the power of human determination and the impact one individual can have on advancing medical science. His journey from a hopeful athlete to a medical researcher fighting a rare disease offers both inspiration and a call to action for continued innovation in healthcare.

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Notable Quotes with Timestamps:

• [00:04] David Fajgenbaum: "I'll never forget my doctor walking into the room and saying, David, your liver, your kidneys, your bone marrow, your heart and your lungs are shutting down."

• [04:45] David Fajgenbaum: "It completely shaped my desire to become a doctor... this is what I have to spend the rest of my life doing."

• [09:11] Grant Mitchell: "A priest came in and read him his last rites. And David, what? You're not going to die."

• [25:12] David Fajgenbaum: "What if there's some other drug out there that wasn't made for Castleman disease... could save my life?"

• [37:02] David Fajgenbaum: "It's because we connected on that last one that I'm still here and that now I can continue to pursue this for other people."

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About the Hosts and Contributors:

Symptomatic: A Medical Mystery Podcast is produced by Ruby Studio from iHeartMedia, with Lauren Bright Pacheco as the host. The episode was executive produced by Matt Romano and Lauren Bright Pacheco, with post-production by James Foster, and research conducted by Diana Davis.

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Looking Ahead:

In Part 2 of this series, listeners will follow David's continued efforts to combat Castleman Disease as he aids another patient, Gary Gravina, highlighting the ongoing challenges and triumphs in the fight against this elusive disease.

Transcript

[David Fagenbaum]

I'll never forget my doctor walking into the room and saying, david, your liver, your kidneys, your bone marrow, your heart and your lungs are shutting down. I was just treating patients down the hall.

[Caitlin]

I was just spiraling, not knowing what was actually happening, just being so confused because I had just talked to him, like, two days ago.

[Grant Mitchell]

A priest came in and read him his last rites, and then a few of his friends came in and ultimately hugged him goodbye.

[David Fagenbaum]

I had to take some action, and it had to be, like, a crazy step, and that is to start testing one of these drugs that I was studying in the lab on myself.

[Lauren Bright Pacheco]

How terrifying would it be to fight an unknown enemy, one you didn't recognize and didn't see coming? What if that enemy was coming from within? A disease that even doctors couldn't identify? Nearly half of all Americans suffer from some chronic illness, and many struggle for an accurate diagnosis. These are their stories. I'm Lauren Bright Pacheco, and this is symptomatic. David Fagenbaum grew up in Raleigh, North.

[David Fagenbaum]

Carolina, and I've got two older sisters, seven and five years older than me, and two amazing parents. They immigrated to the United States from Trinidad and Tobago and the Caribbean. So they were sort of making this new life the American dream in the States.

[Lauren Bright Pacheco]

And childhood exposure to a very American sport ignited one of David's biggest dreams. And your dad is an orthopedic surgeon and worked for a period of time with North Carolina State Wolf Pack team.

[David Fagenbaum]

That's right.

[Lauren Bright Pacheco]

Which is where at the age of seven, you had this burning desire to play which position in what division?

[David Fagenbaum]

I wanted to play quarterback, and I wanted to play Division 1 college football. That was like my first dream. And that is all I could think about for about a decade.

[Lauren Bright Pacheco]

Your dad working so much, your mom kind of became almost your football trainer.

[David Fagenbaum]

She did. She was my football trainer. She was my mom, obviously. She was also one of my closest friends. And there was a hill behind our house, and she would stand at the top of this hill, and I'd throw the football into the hill, and then she could, you know, throw it back down. She just wanted to help me in any way that she could, even if it was just, you know, rolling footballs down a hill.

[Lauren Bright Pacheco]

At an early age, David showed his ability for extreme dedication and focus, becoming a star high school quarterback. But that's just one of the reasons he caught the attention of Caitlin, his future wife.

[Caitlin]

He was the president of student council, and we had morning meeting. Every morning he got up there with his best friend, and nothing to do with school at all. They started rapping Eminem songs. The whole student body was just like, what is happening? And I even said that. I'm like, I was very confused by him, but I was also like, wow, he's really attractive.

[Lauren Bright Pacheco]

Attractive and driven. You ended up playing quarterback for Georgetown.

[David Fagenbaum]

That's right. Listeners may not know Georgetown has a football team, but we do, and we are Division One. Yes. For me, it was the ultimate dream that I. Yeah, I'd been thinking about for over 10 years.

[Lauren Bright Pacheco]

It's bittersweet, too, because I know that your mom was diagnosed your freshman year.

[David Fagenbaum]

That's right. Actually, just two weeks after she dropped me off to Georgetown. And I got this phone call from my dad. When he called, I started telling him all about this football practice we had and all these touchdowns and all this stuff, and he was just silent. And then he told me. He said, david, your mom has brain cancer. And, gosh, I was like, what? You know, that. That can't be Mom. Like, she's. She's the most amazing person to everyone. Like, it's not fair. It's not right. And so, yeah, that. That sort of changed everything in my life. It just. Everything changed.

[Lauren Bright Pacheco]

Your family did exactly what, in an ideal world, any family would be able to do. You were really there, and you were so present for her. Did it shape your desire to become a doctor?

[David Fagenbaum]

It completely shaped my desire to become a doctor. I mean, the moment that I heard my mom had cancer, and of course, the moment that I saw her dealing with her cancer, I just said, this is what I have to spend the rest of my life doing. And by this, it's taking care of people with horrible diseases, and it's searching for treatments so that people don't suffer. Like I witnessed my mom suffering.

[Lauren Bright Pacheco]

You know, I can't imagine how painful. Because you were 19 when she passed.

[David Fagenbaum]

I could go on all day about her. She was such a force. She battled brain cancer for 15 months, just so valiantly. And everything about it, you know, I share about the humor that she brought into it. You know, the very first brain surgery she had, you know, we were devastated going into that surgery. You know, what's mom going to be like coming out of this? Is she going to be the same person? So we all go back to see her, and I remember that they pulled this curtain back, and she had this wrap around her head, and then she had this tube coming out of the incision, and it had sort of a bulb at the end. It was actually collecting the fluid. She looked at us, and she pointed to her head and she said, chiquita banana lady. And we just like, burst into laughter. It was what we needed. But my mom's passing, it impaled me and then it set me on fire.

[Lauren Bright Pacheco]

David's focus now set on medicine. He graduated from Georgetown and was attending the University of Pennsylvania for his medical degree. And although no longer leading a football team, his drive for physical fitness continued.

[David Fagenbaum]

I continued to exercise a lot and, and that was just an outlet that I loved. And so as a result, I, I became like, really fit.

[Lauren Bright Pacheco]

And you had a nickname because of it?

[David Fagenbaum]

Yes, I was called the Beast because I was in really good shape. I won a bench pressing contest. In fact, I set the Virginia state record for bench pressing, which, if you were to look at me now, you'd be like, are you sure about that? Because I definitely am not going to set any bench pressing records these days.

[Grant Mitchell]

He was really one of the healthiest guys I'd ever met. We'd go to the cafeteria and he'd get a piece of chicken and pick the fat off the chicken even, because he was so particular about what was going into his body.

[Lauren Bright Pacheco]

That's Grant Mitchell, David's longtime friend, colleague, and college roommate.

[Grant Mitchell]

So in medical school you do rotations in different hospitals. And we got posted out for our OB GYN rotation in Bethlehem, Pennsylvania, outside of Philadelphia. And we were staying in some dorms there and there was no gym. And so that was not going to stop David from working out. And so we found a tree outside of the dorm there that had a nice branch.

[David Fagenbaum]

The tree branch, it just looked too perfect. It was horizontal, it was perfect.

[Grant Mitchell]

So we could hang from and do pull ups from.

[David Fagenbaum]

And so, yeah, every time we walked past this tree, we had to do pull ups before we went to treat patients. So, yeah, we had to get pull ups in every morning.

[Lauren Bright Pacheco]

And in a weird way, that tree branch ended up being an indicator that you were getting sick.

[David Fagenbaum]

You're right, because as the weeks went on, I stopped wanting to do the pull ups. I didn't have the energy to do the pull ups. I actually hadn't thought about that until you mentioned that now. Yeah, I couldn't do them. I was just dragging.

[Lauren Bright Pacheco]

At this point in his third year of medical school, David's mental focus was on his residency and passing exams. But suddenly, and quite out of character, David was having trouble keeping up physically.

[David Fagenbaum]

Then the fatigue became this fatigue that I'd never experienced before. It was like this insatiable fatigue, basically. Like no matter how much I slept, I just was exhausted. I Couldn't get out of bed. I noticed lumps and bumps in my neck and fluid around my ankles. And I didn't want to go there mentally, but I knew that if a patient walked into my office, I was a third year med student patient walked into my room and I'm the doctor looking at them, I would have been very concerned and I would have specifically said, I'm very worried that you have an aggressive lymphoma and such an aggressive lymphoma that, you know, you might have a few weeks to live. It was moving so rapidly, but I was like trying to just block that out of my brain while at the same time I knew something really bad was happening. I even told Grant one day he.

[Grant Mitchell]

Walked into the living room of our apartment and he said, something is just wrong. I think I'm going to die. And David, what? You're not going to die. Like, what's gotten into you?

[Lauren Bright Pacheco]

How did you process that? Maybe just the stress of med school getting to him.

[Grant Mitchell]

Yeah, I just thought that, you know, he was focused on health and I didn't think much of it. Just told him to, you know, relax, it's okay. A lot of medical students go through this when they are in medical school and they're learning thousands of different ailments that can occur in the human body. And you start sort of thinking about what's going on inside of you and even get a little sense of paranoia. And over diagnosis. It's kind of a running joke within medical school. Everyone's sort of diagnosing themselves and all the different things that could be happening. And so I just thought it was.

[Lauren Bright Pacheco]

That in addition to the exhaustion and swelling, David was noticing rashes and redness popping up all over his body. It was clear that whatever was going on, it needed immediate attention. But David, being hyper focused, was determined to make it through his OB GYN exam before turning his attention towards himself.

[David Fagenbaum]

I remember while I'm taking the exam, just like full body sweating, I'm like shivering. I like can't keep my eyes open. But I went from taking the exam and I went down the hall and I just, I went straight to the er and they took me back almost immediately. They just, I just was. I was so ill and they did blood work and I'll never forget my doctor walking into the room and saying, david, your liver, your kidneys, your bone marrow, your heart and your lungs are shutting down. We have to hospitalize you right away. And I'm like sitting there, I'm like. But I was just treating patients down the hall, like a couple days ago.

[Caitlin]

We were taking a break at this point, and I remember being on Facebook and seeing a lot of people writing on his page. I'm praying for you. I'm thinking about you. So I was wondering what was going on.

[David Fagenbaum]

I hoped that it was maybe some virus, because, you know, viruses come and go. You might get really sick, but it'll be gone at some point. We hoped it was a virus, didn't turn out to be a virus. We then thought, maybe it's not autoimmune disease. But none of the autoimmune disease tests were coming back. And then that sort of left us with, like, what's the other thing that could be causing this sort of the big bad, scary thing? And that was lymphoma. But the tests we were doing weren't giving us an answer. And that was actually one of the last really vivid memories I have from what then turned into hospitalization, where I just became more and more confused and less and less aware of what was going on.

[Lauren Bright Pacheco]

David and his family found themselves in an all too familiar and painful situation, gathered around a hospital bed, only this time, David as the patient. Doctors performed a bone marrow biopsy, PET scans, MRIs, a liver biopsy, among other tests, none of which provided clarity around the cause of these symptoms. David was given high dose corticosteroids, a common practice in the ICU when there is no clear path to treatment. And as the days and weeks progressed, David's illness was impossible to ignore.

[David Fagenbaum]

The physical morph was pretty incredible, and sometimes you, like, have to see the pictures to really understand. But I'll try to describe what happened to me. So because my liver and my kidneys stopped working, what happens is you start gaining fluid all over your body. So I gained what we estimate to be close to a. Now imagine at the same time, you're not eating because you're so sick and you can't keep down any food, and your immune system is literally ravaging all your vital organs. So as a result, you lose all of the muscle mass and any lean mass that you have. So you're left with a body that has 100 pounds of fluid, has lost 50 to 60 pounds of muscle. You're just bone and fluid everywhere. You're just like a swollen, you know, skeleton. Basically, that's what I looked like.

[Grant Mitchell]

The pictures that we have of him in the hospital are not even close to how bad it was. And the reason for that was because David didn't want any pictures. That's not how he wanted to Be remembered. David thought he was dying.

[Lauren Bright Pacheco]

David was airlifted back to his hometown to the hospital his father worked out of. He spent seven more weeks there until he improved just enough to be discharged, only to find himself right back where he was one month later. After months of testing and hospitalization, David had a lymph node biopsy, which returned some surprising results.

[David Fagenbaum]

I wasn't talking. I wasn't doing anything. I was just laying there. So imagine there's 11 weeks of, like, my dad and my two sisters just being there for me through everything, helping me to breathe when I didn't want to breathe, like, just fighting for my life. And the first moment where, like, the three of them are not in the room is like, the moment when this nurse comes in. So she's like, you know, I got the news. I just figured I'd deliver it to you. And she's like, good news. It's not lymphoma. And then she looks at the piece of paper because she doesn't know what the word is. She's never seen it. She's like, you have something called Castlemans. I'm like, well, is that good? Is that bad? She's like, well, it's not lymphoma. Like, it's great, I guess. And so here I am by myself, and I'm like, great. It's like Castleman's like, I don't. I'm a med student, but I don't remember learning about it. I think maybe I heard it once in my life.

[Grant Mitchell]

So, good news. We know what it is. So what do you do when you first hear about something and you want to learn more? You Google it. Then you see the Wikipedia page.

[David Fagenbaum]

The way that it was described was that it was just uniformly fatal, and everyone died within a couple years of diagnosis. And I was just devastated to read about this disease.

[Lauren Bright Pacheco]

Castleman disease is a rare condition that causes the immune system to go into hyperdrive, attacking organs and bodily pathways. In the United States, there are only about 5,000 new cases annually, with each prognosis varying based on the subtype. David was unfortunately diagnosed with one of the most aggressive variations. Desperate to quickly find a treatment that worked, David was transferred to the hematology and oncology ward at Duke in Durham, North Carolina.

[David Fagenbaum]

When I was at Duke for my second hospitalization, I was so sick that my doctors encouraged my family to say goodbye to me.

[Grant Mitchell]

It was shocking. You know, we were still very young. It was the time in our lives where we were energized to, you know, we were healthy. We were young. We were ready to go, you know, conquer the world. And to see the person among us that seems the strongest transformed so abruptly was startling. It was. It was hard to process.

[David Fagenbaum]

We.

[Grant Mitchell]

I didn't think it was even real. Like, surely, he'll just be fine soon. And that changed dramatically for us when they ultimately told him that they didn't know what else they could do. I'll never forget the moment when a.

[David Fagenbaum]

Priest came in to read me my last rites. That was in November of 2010. I was 25 years then.

[Grant Mitchell]

A few of his friends came in and ultimately hugged him goodbye. And I think everyone tried to keep a positive outlook, you know, you're going to be okay. And I remember I couldn't really keep it together. David and I talk about that a lot. He says that he almost knew how bad it was when I came in the room and you saw my face because I couldn't hide how horrifying it was to see him in that state.

[David Fagenbaum]

Yeah. And when you administer your last rats, when you say goodbye to your family, you don't do it like, thinking that, I'm gonna get another shot at this. It's like, this is it.

[Lauren Bright Pacheco]

David, who had been the physical ideal of athleticism and health just months before, was now unrecognizable. Seemingly at the end of his fight with Castle, Caitlin traveled to visit him in the hospital. Despite no longer dating at the time, there was still a connection between them.

[Caitlin]

If this was gonna be the last time. I wanted to talk to him, just to hold his hand, to see how he was doing.

[David Fagenbaum]

I can barely form sentences. I don't know what the heck's going on. I'm confused. And this is gonna be the last time Caitlin's gonna see me. I'm not gonna be able to tell her the things that I want to tell her. So she came to visit me multiple times. And each time, I somehow communicated to my sisters that I didn't want her to come in the room.

[Caitlin]

I thought that maybe he didn't know that I was trying to see him because, you know, I had his phone number, and I would reach out, and I just, you know, wouldn't hear back from him. So then I would reach out to his sisters and just see. And I did think that, like, they were. Maybe they were mad at me because I broke up with him. And, you know, I thought maybe there was, like, something, like, petty, but, like, there wasn't. They were just protecting their brother.

[David Fagenbaum]

I regret that, because who cares if I didn't look like my former self? And who Cares, you know, if I didn't say the right words.

[Lauren Bright Pacheco]

David had now come to the brink of death twice in a span of three months.

[David Fagenbaum]

Turned out that there were no FDA approved drugs, but there were a couple drugs that had been tried, particularly chemotherapies. And one of them worked for a little bit of time and then I started to relapse.

[Lauren Bright Pacheco]

While the chemo suppressed David's immune system, stopping Castleman from attacking his body, it also took a heavy toll on David's ability to fight. But there was one last hope waiting for him in Arkansas.

[David Fagenbaum]

I learned that there was. The world's expert was in Little Rock, Arkansas. So I traveled out to the Mecca of Castleman disease. I've been given the plan, like I'm going to be on an experimental drug. It was going, undergoing a clinical trial and everyone and was working for a bunch of people and I was like, oh my gosh. Like, you know, we'd been praying for this for my mom and we never got it. But now here we were. For me, like maybe we got this. This is like the drug we've been waiting for. And you know, just before I was supposed to fly back to North Carolina, which is where my family lives, to recover, the test results came back from my Little Rock visit. That my labs were all horrible and my organs were all shutting down again. So we actually were, we were actually in the airport in Little Rock getting ready to leave and then we just went back to the hospital. That was the beginning of about a seven week long hospitalization where I sort of went off the cliff again.

[Lauren Bright Pacheco]

My gosh, you. You had to go through this cycle so many times. How did you find the strength in those moments to just keep going?

[David Fagenbaum]

Yeah, I think for me there were a few things that helped me to keep fighting. I mean, for one, I felt like I had this unfinished business to do. Like I promised my mom I was going to find drugs for people suffering from diseases. And I'm a third year med student. I'm sort of like finally somewhat trained to start helping people. And then now I'm going to go out and never be able to do the thing that I promised my mom. Another one was just the amazing support I got from my family. My sisters never left my side, my dad never left my side. I just wanted to be with them longer. Like I just wanted more time with them.

[Lauren Bright Pacheco]

Having traveled nearly a thousand miles to the world's foremost Castleman expert, David recognized the continued cycle of chemotherapy would inevitably catch up to him. That's when things changed. He was no longer content to merely be the patient.

[David Fagenbaum]

My doctor explains to me that like, we've tried everything, there's nothing else that we can do. And I just hit rock bottom. I thought, I'm gonna get to work and try to find a treatment for this disease to save my life.

[Lauren Bright Pacheco]

We'll be right back with Symptomatic A Medical Mystery Podcast.

[N/A]

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[Lauren Bright Pacheco]

Now back to Symptomatic A Medical Mystery Podcast. David Fagenbaum, once a college quarterback and powerlifting champion, was coming out of his third hospitalization from Castleman Disease. After the only known drug to help treat Castleman failed, David went through seven weeks of multi agent chemotherapy, daily blood transfusions and dialysis. David and his family returned home to North Carolina fearful of when the next relapse would begin. But this time he had a little extra support.

[David Fagenbaum]

So at this stage, this is when I had lost my hair from chemotherapy. I still had about 50 pounds of fluid all over my body. My belly, you know, was indistinguishable from someone who would be eight months pregnant. And Caitlin, she was my door.

[Caitlin]

I didn't know how bad it was when I was there because no one Gave me the details. When I was reaching out to his sisters, no one said, this is it. He's being read his last rites. I didn't find these things out until later, which almost helped. It kind of helped me cope.

[David Fagenbaum]

And she said to me, I want us to get back together. I had been hoping for that for so long, but here I am with, like, this horrible, deadly disease. I don't think any human could have more baggage than I had at that moment. Just being like, are you sure? Like, you know, I got a lot going on, you know, got this horrible, deadly disease. Like, are you sure? And she looked at me like she was offended that I was asking her that. Like, of course. Like, are you kidding me? Like, of course I want us to get back together. And it was like, that's exactly what I needed. In that moment.

[Caitlin]

I knew it was him. It was still him in there. So it just didn't matter. The physical appearance.

[Lauren Bright Pacheco]

Is there a moment that you look back where you worried? Because it was just too much for David.

[Caitlin]

I mean, it was definitely when his doctors said that they've tried everything and there was nothing else that they could do. That's when Dave was like, I gotta take this into my hands. What can I do for myself if.

[David Fagenbaum]

I'm gonna hope for a drug to save my life? Like, shouldn't I be acting or, like, doing something to get there? So for me, it was okay. I'm going to get involved in research. I'm going to build an organization called the Castle Collaborative network. I'm going to start conducting laboratory research myself, and I'm going to get to.

[Caitlin]

Work in Dave fashion. That's how he copes. He's going to fix it. So we were his doers, and he was the fixer. While he's in the hospital bed having ice packs under his arms because he has fevers.

[Grant Mitchell]

And for someone who is as focused as Dave, there's nothing that will focus you more in this life than staring down that clock. You know, we call it a dream team, but, you know, David was the engine. David was the force behind it all.

[Lauren Bright Pacheco]

He was quarterbacking it.

[Grant Mitchell]

Absolutely. He slotted right in in that role.

[Lauren Bright Pacheco]

David spent the next six months at home regaining his strength. And although the experimental drug Ciltuximab that David had taken failed to help him recover, he was now using it in hopes that it would work as a preventative measure. He returned to medical and got to work on finding a cure for Castleman.

[David Fagenbaum]

We weren't just going to hope that Santa's elves were going to like magically come up with some brilliant idea and do the research, we simply said, what should we do? We asked everyone that. And then we simply found the best people in the world to do the things that were prioritized to us. So that was one major shift. And the other one was again, a very simple realization. And that was it cost between 1 and $2 billion to create a new drug from scratch, and that can take 10 to 15 years for one drug. So I didn't have a billion dollars, I didn't have 10 to 15 years. So I said, okay, well how else could I potentially be treated? Well, all those chemotherapies that I got that saved my life, they weren't made for Castleman disease. What if there's some other drug out there that wasn't made for calcium disease? I mean, the chemo doesn't work long term, but it's saved my life a few times. I appreciate the chemo. Is there something else? So that became my mission. Can I figure out what's going wrong in my body and then can I figure out, is there a drug that's already FDA approved for some other disease that might actually be able to be useful for my disease that I thought could save my life?

[Lauren Bright Pacheco]

David recruited experts from all over the world to join the Castleman Disease Collaborative Network, or cdcn, and diligently continued his lab research to understand what was happening in his body. Despite all the effort toward finding a cure, David experienced a fourth relapse in April of 2012. After his longest stretch of stability, the now standard playbook for a flare up, David gets a massive round of chemo, all while trying to maintain some sort of normalcy in his life.

[David Fagenbaum]

So at this stage, Caitlin and I are engaged. We're engaged to get married on May 24, 2014. And I know that I'm not going to make it there at the current rate. I actually real my last relapse was while I was getting weekly chemotherapy for the first time ever. We were like, let's try preventative chemo, which is not a thing, but let's try it like in advance and see if that'll stop it. And it still roared its head, it still exploded, still put me in the ICU for a month. So that didn't work.

[Grant Mitchell]

It's impossible to work backwards from there to figure out what went wrong that led to it. And it occurred to us that instead of taking samples from his blood while he was in the throes of these flares, we should take those samples before and after and we should do it every few weeks so that we can study maybe the progenitor markers of what is initiating this cascade. And if we can find out what's going on early, before it goes full blown, maybe we can stop the cascade from ever occurring.

[David Fagenbaum]

I've said goodbye to my family five times, and this thing's going to keep coming back. So if I wanted to make it to May 24, 2014, I had to take some action, and it had to be a pretty, in hindsight, like, sort of crazy step, and that is to start testing one of these drugs that I was studying in the lab on myself.

[Caitlin]

And I was like, what are the side effects? You know, he was like, it could either work or, you know, it doesn't work. So I just, I. I was very confused. I was like, are you sure, like yourself, you're going to try this on yourself? And so I was very unsure about it. I didn't have a lot of faith that this was going to work. I felt like we were just going to be in the same place 15 months later.

[Lauren Bright Pacheco]

Was that your biggest fear?

[Caitlin]

Yeah, that it was just going to be a cycle.

[Lauren Bright Pacheco]

As David battles Castleman disease for the fifth time, he starts to put his research to the test. Trying drugs that will target the immune system. First on the list, David started taking cyclosporine. While he showed no signs of improvement, his condition didn't worsen, which seemed positive. He then moved on to the second drug. IVIg helped David feel better almost immediately. Blood tests were finally heading in the right direction, only for Castleman disease to knock David down once again. A few weeks later, it was back to the old playbook, and David had to undergo a new. Another massive round of chemo.

[David Fagenbaum]

There were some real heartbreak, right? It was like, Caitlin, I've been doing this work in the lab. I've been experimenting on my own blood samples. I've been experimenting on lymphoid tissue. That's like the moment where you want to try these drugs to see, like, while you're getting worse, like, does it stabilize things? And it didn't. And that was heartbreaking.

[Grant Mitchell]

And the tricky thing about this disease is that you don't necessarily know if it's working or not until you don't have a flare. So you have to wait. And these flares would happen about every year. So let's say a flare occurs and then you realize the drug that you're on didn't work. And now you try a new drug after the flare subsides. And it doesn't just subside you have to obliterate your immune system with 7 agent chemo to stop it. And then once you survive that onslaught of toxic drugs, you say, okay, now we'll try a new drug.

[David Fagenbaum]

And I don't know how I survived that fifth one. They gave me like humanly impossible doses. I was like taking like large animal doses of chemo. But I knew that it wasn't going to work long term.

[Lauren Bright Pacheco]

I can't imagine watching someone you love suffer the way he obviously suffered with all of those relapses. But particularly in the case of the chemo, the treatment seemed even worse than the disease. How grueling was it to watch him go through a cycle of relapses?

[Caitlin]

It was just like such a letdown when you would think like, he just did the chemo and now he's been better for 16 to 18 months and then all of a sudden, you know, it happens again. It was just so frustrating. Like, how many times can a body get this much chemotherapy?

[Lauren Bright Pacheco]

After recovering from his fifth barrage of chemo, David looks at the last option on the table. From his research, getting to know Castleman disease. Through their experimentation, Grant and David learned that his subtype causes the bodily communication line called MTOR to go into overdrive. MTOR tells the immune system to mobilize and activates T cells to go to war, attacking foreign cells, or in David's case, his own.

[David Fagenbaum]

I thought that, hey, why don't use an MTOR inhibitor? I mean, again, it was very simple as there was too much. This communication line looked like it was turned into overdrive. Here's a drug that turns it off. Let's try it.

[Grant Mitchell]

We were at a point where there was a no regret movement to try something else. And that was something called sirolimus. It is isolated from a fungus found in the soil of Easter Island. It hits the MTOR pathway and reduces T cell activation. Maybe it could prevent the cascade that ultimately led to the cytokine storm that would attack his body.

[David Fagenbaum]

This was the third and frankly, probably the last possible attempt. There weren't many more drugs on our list of possibilities and there wasn't much more time. So it probably was the last ditch effort after like many last ditch efforts.

[Lauren Bright Pacheco]

Now taking the only medication left on the table, David and Caitlin did have something worth looking forward to their wedding. But what was weighing on David's mind? The issue of the hair on his head, or lack thereof.

[Grant Mitchell]

I remember we were in the hotel room getting ready for the wedding and he had just started to grow his hair back. He was so Protective of every hair on his head. You know, it didn't look good. It was just kind of like, thinly there and a little bit on his neck. And, like, I was like, david, let me just shave these hairs on the back of your neck and so you can look nice and trim for your wedding day.

[David Fagenbaum]

And I told him absolutely not, because my hair had just come in. Like, I got, like, my hair started to grow, like, two weeks before my wedding day. So it kind of looked like I just had this, like, very short buzz cut or something. But. But yeah, I had. I had. Your neck hair had grown back, and Grant's like, let me clean you up. It's your wedding day. I'm like, no, like, every. Every follicle matters. Like, you're not there. There is every hair that is on my head. It is staying there.

[Lauren Bright Pacheco]

I love that.

[Grant Mitchell]

But it was just awesome because, like I said, after I hugged him goodbye that day, I didn't think I'd ever see him again.

[Lauren Bright Pacheco]

Having already been through until death do us part, what did it mean to exchange vows? What did your wedding mean to you? On a deeper level?

[Caitlin]

It was so powerful. It was like those words were so real, where I feel like people just say those as their vows, but really we meant them so much to each other. We had already been through it.

[David Fagenbaum]

Yeah.

[Caitlin]

It just meant so much to us.

[Lauren Bright Pacheco]

As David and Caitlin now look towards the future, they couldn't help but be troubled by lingering thoughts of fear. Will Castleman disease return? And if so, what other possible options are left on the table?

[Grant Mitchell]

We didn't know right away if it was working or not.

[Caitlin]

We kind of just waited each month and were like, is it coming? Is it coming?

[Grant Mitchell]

We had to wait a full year to see if he was going to undergo another flare. So eight months go by. We're on the edge of our seat. 12 months go by. We're watching and waiting. 14 months, 16, 18.

[Caitlin]

19 months. 20 months, 21 months.

[Grant Mitchell]

Two years go by.

[Caitlin]

It wasn't coming back. We were kind of like, oh, my gosh, something's working.

[Grant Mitchell]

Months and months after. Longer than he'd ever been in remission or not in flare. My God. My God. He's okay. We think we found a cure.

[David Fagenbaum]

The s. That's the one that works. And that's why I'm here and I'm on this podcast, right? If it didn't work, I'm not here 10 years ago. This is when I pass. And I'm very much a memory for Caitlin and my family. But it's because we connected on that last one that I'm still here and that now I can continue to pursue this for other people.

[Lauren Bright Pacheco]

How did this shape your perspective once it went into remission, if I may use that word?

[David Fagenbaum]

Yeah, absolutely. I do like to use that word. And ever since this remission started, I just have this feeling of overtime. It's like, okay. I don't know when the disease could come back. Of course, as more and more days go by, the more confident I feel that maybe we've really gotten this disease under full control. But it's just given me this urgency where it's like, I gotta do as many things as I can do.

[Caitlin]

When we finally got off the hamster wheel, yeah, it was just like, I can just, like, feel it. Even saying it to you right now. I can feel, like, weight just coming off my chest. Like, in that moment, we were so relieved.

[Lauren Bright Pacheco]

David Feigenbaum was pushed to the brink of death five times before finally finding a medicine that sent his Castleman disease into remission. David and Kaitlyn didn't just make it to their first wedding anniversary. They're now celebrating their 10th and counting, along with the two adorable children they welcomed along the way.

[Caitlin]

We're just so much more grateful for the small things. Amelia's having her preschool graduation, and now Dave gets to be at, like, her preschool graduation. So, like, huge milestone for our family. We're just so grateful for that. Just having him be able to come to her dance recital. We're just so grateful that we are in this overtime for our family. And I truly believe our overtime is going to go on for a long time.

[Lauren Bright Pacheco]

Just as living through his mother's cancer treatment pushed him to study medicine, living through Castleman disease lit a new fire within David.

[David Fagenbaum]

You know, after finding out that sirolimus could save my life, all I've been able to think about for these last 10 years is how many more drugs are sitting out there. They could be life saving for other people. I mean, I was walking back and forth past this CVS that ended up being the place where I got my sirolimus from. For years, it was always there. And for years, I'm sick with this horrible disease. I'm in the icu, and then I'm home, and then I'm back in the icu. And all along, that pill bottle with sirolimus in it had been there because it's approved for kidney transplant rejection, and it's utilized by people all over the world, but it's not used for Castlemans. And it's like, oh, my Gosh, how many more of those drugs at your CVS could be life saving for you or someone you love? I mean, like, what is the untapped potential within our medical system?

[Lauren Bright Pacheco]

And Grant, you decided to join him in this pursuit?

[Grant Mitchell]

Yeah, and we called all the researchers in the world that might know anything about this disease. There were only 20 of them or so, and we invited them all to a conference. And I'll never forget sitting there at the head of the table with David, said, this is David and I'm Grant, you know, and we're here to cure Castleman disease. And just seeing these researchers who had been at this for years around the table kind of chuckle and say, okay, kids, good luck, we'll try and be helpful. It was just one of those moments where we were young and naive enough to have the audacity to think that we could do anything.

[Lauren Bright Pacheco]

Unlocking the off label potential of approved medicines will quickly be put to the test in part two of David's story. Join us next week as David crosses paths with another patient battling Castleman disease, Gary Gravina, who is clinging to life during a terrifying flare up.

[Gary Gravina]

My wife started to notice that my stomach was getting larger and I wasn't really eating because I felt so ill. And so for me to be putting on weight was weird. I'm taking, well, this is going to be something really simple and they're going to take care of it. And then when they started talking about admitting me, I'm like, come on, this is not something like that. I don't need to be in the hospital. This is ridiculous. By the end of that week, I was in a medically induced coma.

[Lauren Bright Pacheco]

Having beaten back his own Castleman disease, David is determined to help Gary fight his.

[David Fagenbaum]

I'm told, hey, there's a patient with your subtype of Castleman's, this very rare subtype. All of his organs are obviously failing and he looks just like me when I was at my sickest. I remember telling him that, you know, we're going to beat this.

[Lauren Bright Pacheco]

But when David's course of action for Gary doesn't work, they find themselves thrust into the same desperate race against time. David knows all too well I was.

[Gary Gravina]

In a coma and I was just, you know, everything in me was tanking. All the things are connected to you and you're just kind of, you feel apart from everything and I can just remember crying tears of frustration.

[Lauren Bright Pacheco]

Symptomatic Medical Mystery Podcast is a production of Ruby Studio from iHeartMedia. Our show is hosted by me, Lauren Bright, Pacheco executive producers are Matt Romano and myself. Our EP of post production is James Foster. Our producers are Sierra Kaiser and John Irwin and this episode was researched by Diana Davis.

[N/A]

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